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Health and Energy Flow and Enzymes

You are sitting in the doctor's office with a killer sore throat and feeling like you would rather sell your soul, even if it meant taking a biology exam every day, in exchange for a stop to the throat-throbbing pain. To make matters worse, the doctor looks into your throat and gives you a nice pat on the back and says, “Don’t worry, you’ll be fine. Grab yourself some chicken soup and weather this one out in bed.”

You think to yourself, “What? Are you kidding me? No pill to make this go away? No antibiotics? Oh well. At least I get to miss the rest of the school day.”

While you may feel that your doctor is acting with gross incompetence, it turns out that he is following good medical practice. Antibiotics have been widely over-prescribed in recent years, and the consequence of this is worldwide drug resistance. Heck, in some instances, antibiotics were prescribed for viruses, for which they have no effect.

Antibiotic resistance occurs when the drug is no longer effective at killing the microbe that is making you sick. If you think that this sounds like a frightening prospect, you are dead right. It may very well happen that sometime in the future, when you really need antibiotics to work—after surgery or wound infection are two good examples—the antibiotics you take may not do a whole lot of anything. You might as well buy them a cable package and plop them in front of your 52" flat screen.

The discovery of antibiotics has had a huge positive impact on human health, for sure, but the possibility that these drugs may lose their effectiveness is scarier than Final Destination 5. Studies have shown that patients who were prescribed an antibiotic by their primary care doctor are more likely to have problems with bacterial resistance for up to 12 months afterward.4 Sucks to be…us.

Understanding antibiotic resistance involves more than just knowing how antibiotics work; it also requires knowing about enzymes, microbiology, and evolution. Antibiotics bind to proteins, often enzymes, that are absolutely essential for a pesky microbe's life, and afterward, the antibiotics inactivate them. The antibiotics rifampicin and sorangicin work by binding the RNA polymerase enzyme (the enzyme that produces RNA), impairing its activity.5

Antibiotics can actually be found in nature, meaning that they are natural defense molecules that some microorganisms in nature use against other microorganisms to hurt or kill them. It's a dog-eat-dog world. Many antibiotics target bacterial cellular processes, and these antibiotics are therefore less likely to interfere with the cell functions within your body. Penicillin interferes with enzymes that produce the bacterial cell wall. It binds to the active site of the enzyme irreversibly, and the enzyme is then no longer able to bind to its normal substrate and catalyze the cell wall-building reaction.6 Gotcha, bacteria.

In a nicely demonstrated "I'll show you," microbes become resistant to antibiotics in several different ways. For example, microbes can develop a way to degrade the antibiotic. Microbes can prevent the binding of the antibiotic to its target. Microbes can also modify the basic biology of the target protein such that the antibiotic won’t impair it anymore. Nice, huh?

How do bacteria make these changes to resist the antibiotics? The answer is by acquiring changes in their DNA. A bacterium (a single bacterial cell) can acquire a special change to its DNA sequence that will give it a selective advantage against antibiotics. In a lot of ways, it is like winning the lottery. Just as you buy more lottery tickets in hopes that you will increase your chances of winning, bacteria that acquire many mutations in their DNA are more likely to receive the "magic number" or specific DNA change that confers antibiotic resistance. Antibiotic-resistant DNA sequences can also be transferred from one bacterium to another through a process called horizontal gene transfer.

We all know that fame and fortune have their downsides, and acquiring an antibiotic-resistant mutation is no different. These DNA changes can result in fundamental changes in a protein’s structure. In some cases, this translates to enzymes that do not function as well. A bacterium that has a bacterial resistance gene can actually grow more slowly when no antibiotic is present than a bacterium that does not have the said DNA change.

However, when the antibiotic is around, it provides selection pressure, where antibiotic-resistant bacteria gain a selective advantage that outcompetes the bacteria that do not have the DNA change. In other words, that little special bacterium gets free entrance to the VIP, or VIM (Very Important Microbe), club to grow and multiply in the sweet life while his little friends without VIM passes are left out in the cold. Just remember that the next time your doctor prescribes antibiotics when they are not needed, which he or she shouldn't, he or she is basically encouraging evolution that helps antibiotic-resistant bacteria grow and prosper.